Publication Date:
1991-08-30
Description:
Catalytic antibody technology has been used to explore the contribution of medium effects to the overall rate of an enzyme-catalyzed reaction. An antibody generated against a derivative of 2-acetamido-1,5-napthalenedisulfonate efficiently catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. This unimolecular reaction is not susceptible to general acid-base catalysis but is highly sensitive to microenvironment; thus, it provides a simple chemical model for biologically important decarboxylations. The 10(4)-fold rate acceleration observed for the antibody reflects the kinetic advantage of the low-dielectric environment of the binding pocket acting to destabilize the substrate by desolvation and to stabilize the charge-delocalized transition state through dispersion interactions. These results are pertinent to an understanding of solvent effects in enzymic reactions in general and suggest approaches for developing antibody catalysts for numerous other reactions that involve large changes in charge distribution as the reaction coordinate is traversed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, C -- Kramer, T -- Robinson, S -- Hilvert, D -- GM38273/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1991 Aug 30;253(5023):1019-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1887215" target="_blank"〉PubMed〈/a〉
Keywords:
Anilino Naphthalenesulfonates/pharmacology
;
Antibodies/*metabolism
;
Binding, Competitive
;
Calorimetry
;
Fluorescent Dyes
;
Isoxazoles/*metabolism
;
Kinetics
;
Models, Theoretical
;
Naphthalenesulfonates/immunology
;
Solvents
;
Spectrometry, Fluorescence
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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